Iridium-Catalyzed Regio- and Enantioselective Hydrogenation of 5-Alkylidene Cyclopentenones

The regio- and enantioselective hydrogenation of the CC bond in molecules with two or more CC bonds of the same type is very challenging but highly desirable. Herein, we report a regio- and enantioselective hydrogenation of 5-alkylidene cyclopentenones catalyzed by an Ir/BiphPHOX complex, delivering the corresponding mono- and double-hydrogenated products in excellent results, respectively (5-substituted cyclopentenones: up to 99% yield and 98% ee; 2,4-disubstituted cyclopentanones: up to 99% yield, 16:1 dr, and 99% ee). For the chiral 2,4-disubstituted cyclopentanones, the results of mechanistic studies indicated that both the exo- and endocyclic CC bonds of the substrate can be preferentially reduced with the exocyclic CC bond undergoing hydrogenation more readily. The ester group in the substrate plays an important role in improving the reactivity and controlling the stereoselectivity of the product. The reaction was successfully conducted on a gram-scale, and the hydrogenated product can be readily derivatized.